自发性高血压大鼠四氢生物碟呤治疗后动脉的结构及力学改变

目的：探讨长期四氢生物喋呤（BH4）治疗对自发性高血压大鼠（SHR）血管形态及血管力学性质的影响;方法：选用4周龄雄性SHR36只,随机分为实验组和对照组,每组18只。实验组每周2次腹腔注射BH420mg／kg,对照组注射等容量生理盐水,于实验第4、16和26周龄时各取6只测量动脉收缩压（SBP）,并使用计算机图像分析的方法分别测量主动脉血管零应力状态张开角、压力-直径关系及肠系膜动脉血管的壁／腔比值。结果：至BH4治疗后的第16和26周龄,SHR的SBP明显降低（P〈0．01）;实验组SHR胸主动脉张开角显著减小（P〈0．01）,压力-直径（P-D）关系曲线上移;实验组肠系膜动脉三级分支血管壁／腔（W／L）值减小（P〈0．05）。结论：BH4可以减弱由于长期高血压所导致的血管肥厚和管腔狭窄,恢复血管弹性。     

Effects of hydrogen-rich water and ascorbic acid treatment on spontaneously hypertensive rats

Hydrogen-rich water (HW) has been suggested to possess antioxidant properties of value in treatments of lifestyle diseases and for prevention of latent pathologies. To date, the potential benefits of HW against the deleterious effects of excessive salt intake and hypertension have not been investigated. Here, we first examined the effects of HW or HW supplemented with 0.1% ascorbic acid (HWA) on spontaneously hypertensive rats (SHR) that had been fed a normal diet. In comparison to control rats given distilled water (DW), we found that HW did not significantly influence systolic blood pressure (SBP) or diastolic blood pressure (DBP) in SHR; however, the increase in SBP and DBP were inhibited in the HWA group. Next, four groups of SHR were given DW, 0.1% ascorbic acid-added DW (DWA), HW, or HWA in combination with a 4% NaCl-added diet. SHR fed the 4% NaCl-added diet showed increased hypertension; HWA treatment resulted in a significant reduction in blood pressure. The HWA group tended to have lower plasma angiotensin II levels than the DW group. In addition, urinary volumes and urinary sodium levels were significantly lower in the HWA group than the DW group. Urinary isoprostane, an oxidative stress marker, was also significantly lower in the HWA group, suggesting that the inhibitory effect of HWA on blood pressure elevation was caused by a reduction in oxidative stress. These findings suggest a synergistic interaction between HW and ascorbic acid, and also suggest that HWA ingestion has potential for prevention of hypertension.     

有氧运动改善自发性高血压大鼠肾纤维化的作用*

目的: 研究有氧运动训练对自发性高血压大鼠(SHR)肾脏纤维化影响, 探讨有氧运动对高血压肾损害的保护作用。方法: 8周龄雄性SHR和同龄Wistar京都大鼠(WKY)随机分为4组(n=6):安静WKY对照组(WKY-S)、安静SHR对照组(SHR-S)、低强度运动组(SHR-L)和中强度运动组(SHR-M)。SHR-L组、SHR-M组分别以14 m/min(最大有氧速度的35%)、20 m/min(最大有氧速度的50%)在0°坡度的运动跑步机上跑步,共运动14周,每周5次,每次60 min,WKY-S和SHR-S组安静饲养。14周后,运动训练结束72 h后检测大鼠血压;之后取血和肾脏检测血清肌酐SCr和尿素氮BUN含量,苏木精与伊红(HE)染色观察肾组织形态,Masson染色观察肾组织胶原沉积情况,计算肾脏胶原容积分数(CVF),检测肾脏 AngⅡ、AT1R、TGF-β、α-SMA、CTGF蛋白表达。结果: 与WKY-S组相比,SHR-S组的血压和血清SCr、BUN含量、肾脏CVF水平和AngⅡ、AT1R、TGF-β、α-SMA、CTGF蛋白表达均明显升高(P＜0.05);与SHR-S组相比,SHR-L组和SHR-M组血压和血清SCr、BUN含量、肾脏CVF水平和AngⅡ、AT1R、TGF-β、α-SMA、CTGF蛋白表达均明显下降(P＜0.05)且SHR-M组下降趋势更明显(P＜0.05)。结论: 有氧运动可通过抑制肾脏AngⅡ-AT1R-TGF-β通路,改善自发性高血压大鼠的肾纤维化与肾功能。     

阿托伐他汀对自发性高血压大鼠p27蛋白表达及心肌细胞凋亡的影响

目的：观察阿托伐他汀对自发性高血压大鼠（SHR）p27蛋白表达及心肌细胞凋亡的影响。方法：将12只8周龄的雄性SHR随机分为2组（n=6）;蒸馏水饲养组（DW组）与阿托伐他汀治疗组（ATV组）,并以6只同周龄的正常血压大鼠（WKY）作为对照（WKY组）。分别采用RT-PCR与Western blot法检测p27的mRNA及蛋白表达水平;TUNEL法检测心肌细胞的凋亡;同时计算左室重与体重比,检测血脂水平。结果：阿托伐他汀治疗10周后,ATV组与DW组相比较,其①血脂水平及左室重、左室重与体重比均明显降低（P〈0.01）;②p27的mRNA及蛋白表达水平明显上调（P〈0.01）;③心肌细胞的凋亡率显著增高（P〈0.01）。结论：阿托伐他汀能够上调SHR的p27蛋白表达水平、促进其心肌细胞的凋亡,在某种程度上可能与其改善SHR心室肥厚的效应有关。     

Increased mRNA expression of cardiac renin-angiotensin system and collagen synthesis in spontaneously hypertensive rats

Hypertensive cardiac hypertrophy is associated with the accumulation of collagen in the myocardial interstitium. Previous studies have demonstrated that this myocardial fibrosis accounts for impaired myocardial stiffness and ventricular dysfunction. Although cardiac fibroblasts are responsible for the synthesis of fibrillar collagen, the factors that regulate collagen synthesis in cardiac fibroblasts are not fully understood. We investigated the effects of angiotensin II on cardiac collagen synthesis in cardiac fibroblasts. Cardiac fibroblasts of 10 week old spontaneously hypertensive rats and age-matched Wistar-Kyoto rats were prepared and maintained in culture medium supplemented with 10% fetal calf serum. The expression of mRNA of the renin-angiotensin system (renin, angiotensinogen, angiotensin converting enzyme) was determined by using a ribonuclease protection assay. Basal collagen synthesis in cardiac fibroblasts from spontaneously hypertensive rats was 1.6 fold greater than that in the cell of Wistar-Kyoto rats. Angiotensin II stimulated collagen synthesis in cardiac fibroblasts in a dose-dependent manner. The responsiveness of collagen production to angiotensin II was significantly enhanced in cardiac fibroblasts from spontaneously hypertensive rats (100 nM angiotensin II resulted in 185 ± 18% increase above basal levels, 185 ± 18 versus 128 ± 19% in Wistar-Kyoto rats p < 0.01). This effect was receptor-specific, because it was blocked by the competitive inhibitor saralasin and MK 954. These results indicate that collagen production was enhanced in cardiac fibroblasts from spontaneously hypertensive rats, that angiotensin II had a stimulatory effect on collagen synthesis in cardiac fibroblasts, and that cardiac fibroblasts from spontaneously hypertensive rats were hyper-responsive to stimulation by angiotensin II.Level of angiotensin and renin mRNA expressed in ventricles, and angiotensinogen mRNA expressed in fibroblasts from SHR were higher than those from WKY.These findings suggest that the cardiac renin-angiotensin system may play an important role in collagen accumulation in hypertensive cardiac hypertrophy.     

Effects of chronic quercetin treatment on hepatic oxidative status of spontaneously hypertensive rats

The effects of chronic administration of an oral daily dose of quercetin (10 mg Kg^–1), the most abundant dietary flavonoid, were investigated on hepatic oxidative status in spontaneously hypertensive rats and normotensive Wistar Kyoto rats. Decreased liver glutathione peroxidase activity, increased liver total glutathione levels and increased both hepatic and plasmatic malondialdehyde concentrations were observed in spontaneously hypertensive rats when compared to Wistar Kyoto rats. In spontaneously hypertensive rats, treatment with quercetin for 5 weeks reduced blood pressure, increased glutathione peroxidase activity and reduced both plasma and hepatic malondialdehyde levels. However, none of these effects were observed in Wistar Kyoto rats. In conclusion, quercetin shows both antihypertensive and antioxidant properties in this model of genetic hypertension.     

自发性高血压大鼠多组织炎症状态

高血压是一种慢性血管性疾病,易累及肾、肝、心、脑等组织,引起脑卒中和心、肾损害等并发症.本研究对高血压时肾、肝、心、脑等组织的炎症状态进行了观察.实验采用自发性高血压大鼠(spontaneously hypertensive rat,SHR)和正常血压的Wistar-Kyoto(WKY)大鼠,用RT-PCR和Western blot法观察肾、肝、心、脑等组织炎症相关因子IL-1p、TNFα、ICAM-1、iNOS、C/EBPδ和PPARγ的基因表达;紫外分光光度法观察蛋白质羰基化水平和FRAP法检测组织总抗氧化能力.结果显示(1)SHR组织炎症相关因子表达较对照WKY增强,除IL-1βmRNA在肝和脑的增加不明显外,其余均有显著性差异(P＜0.05);(2)SHR和WKY大鼠肾、心、脑蛋白质羰基化水平(nmol/mg蛋白)分别为8.93±1.08和2.27±0.43、2.23±0.23和0.17±0.02、13.42±1.10和5.72±1.01,SHR明显增加(P＜0.05);而肝脏蛋白质羰基化水平无明显变化;(3)SHR肾、肝、心、脑总抗氧化能力水平显著低于WKY大鼠(P＜0.05).以上结果表明,SHR多个组织(肾、肝、心和脑)均存在炎症因子被诱导和氧化应激反应等明显的炎症状态,提示炎症可能在高血压及其并发症的病理改变中起重要作用.     

血小板源生长因子受体介导的信号转导在自发性高血压大鼠心肌肥大中的作用

为了探索血小板源生长因子 (platelet derivedgrowthfactor,PDGF)受体介导的信号转导在自发性高血压大鼠(spontaneouslyhypertensiverats,SHR)心肌肥大中的作用 ,实验采用Westernblot法检测SHR及其对照WKY大鼠心肌PDGF受体β和细胞外信号调节激酶 (extracellularsignal regulatedkinase1/ 2 ,ERK 1/ 2 )的蛋白表达和ERK 1/ 2磷酸化水平的变化。结果显示 :4周龄SHR的收缩压、舒张压、±dp/dtmax和心肌肥大指数与同龄WKY大鼠相比均无明显差异 ,而 12周龄SHR上述指标与同龄WKY大鼠相比均明显升高 ,表明 12周SHR已发生高血压 ,心脏收缩功能代偿性增强 ,并出现心肌肥大。 4周龄SHR心肌PDGF受体 β和ERK1/ 2的磷酸化水平以及ERK 1/ 2的蛋白表达水平与同龄对照相比均无明显变化 ,12周时SHR心肌PDGF受体 β的蛋白表达较同龄WKY增加 32 77% (P <　　　　　　　　　 0 0 5 ) ,PDGF受体介导的信号转导通路的下游信号分子ERK 1/ 2的磷酸化水平较同龄WKY升高 19 6 % (P =0 0 1) ,表明ERK 1/ 2的活化增加 ,但ERK 1/ 2的蛋白表达水平尚无变化。为进一步明确PDGF受体 β在心肌细胞生长中的作用及其与ERK 1/ 2活性的关系 ,采用PDGF BB刺激培养的乳鼠心肌细胞 ,发现 [3 H]亮氨酸掺入量明显增加 ,ERK 1/ 2的磷酸化水平明     

Effects of different intensities of continuous training on vascular inflammation and oxidative stress in spontaneously hypertensive rats

We aimed to study the effects and underlying mechanism of different intensities of continuous training (CT) on vascular inflammation and oxidative stress in spontaneously hypertensive rats (SHR). Rats were divided into five groups (n = 12): Wistar-Kyoto rats sedentary group (WKY-S), sedentary group (SHR-S), low-intensity CT group (SHR-L), medium-intensity CT group (SHR-M) and high-intensity CT group (SHR-H). Changes in body mass, heart rate and blood pressure were recorded. The rats were euthanized after 14 weeks, and blood and vascular tissue samples were collected. Haematoxylin and Eosin staining was used to observe the aortic morphology, and Western blot was used to detect the expression of mesenteric artery proteins. After CT, the mean arterial pressures improved in SHR-L and SHR-M and increased in SHR-H compared with those in SHR-S. Vascular inflammation and oxidative stress levels significantly subsided in SHR-L and SHR-M (p < 0.05), whereas in SHR-H, only vascular inflammation significantly subsided (p < 0.05), and oxidative stress remained unchanged (p > 0.05). AMPK and SIRT1/3 expressions in SHR-L and SHR-M were significantly up-regulated than those in SHR-S (p < 0.05). These results indicated that low- and medium-intensity CT can effectively reduce the inflammatory response and oxidative stress of SHR vascular tissue, and high-intensity CT can improve vascular tissue inflammation but not oxidative stress.     

自发性高血压大鼠和Wistar-Kyoto大鼠心血管组织肾上腺髓质素和肾上腺髓质素原N-末端20肽的水平

本工作观察了自发性高血压大鼠 (SHRs)和Wistar kyoto (WKY)大鼠心肌和主动脉肾上腺髓质素 (a drenomedullin ,ADM)和肾上腺髓质素原N 末端 2 0肽 (proadrenomedullinNterminal 2 0peptide ,PAMP)的水平。以放射免疫分析方法测定血浆、心肌和主动脉ADM含量。用竞争性定量逆转录多聚酶链式反应 (RT PCR)方法测定心肌和主动脉ProADMmRNA含量。结果发现 ,SHRs心肌和主动脉ProADMmRNA水平分别比WKY大鼠高 66 7%和 73 % (均P <0 0 1)。SHRs血浆、心肌和主动脉ADM ir含量分别较WKY大鼠高 2 9%、76 7%和 79% (均P <0 0 1)。SHRs血浆、心肌和主动脉PAMP ir水平分别较WKY大鼠高 42 5 % (P <0 0 1)、47 2 % (P <0 0 1)和 2 7 3 % (P <0 0 5 )。另外 ,SHRs的ADM和PAMP的比值较WKY大鼠明显增高 (心肌和主动脉分别为 2 0± 0 2 5vs 1 64± 0 3和 2 2± 0 18vs 1 5 6± 0 2 8)。结果提示 ,SHRs心肌和主动脉ProADM基因表达上调 ,ADM和PAMP水平升高 ,但二者升高的比例不一致。SHRs的ADM和PAMP升高不一致的病理生理意义有待进一步研究     

Early postnatal changes in sarcoplasmic reticulum calcium transport function in spontaneously hypertensive rats

This comparative study investigates the relationship between sarcoplasmic reticulum (SR) calcium(Ca²⁺)-ATPase transport activity and phospholamban (PLB) phosphorylation in whole cardiac homogenates of spo`ntaneously hypertensive rats (SHR) and their parent, normotensive Wistar Kyoto (WKY) strain during early postnatal development at days 1, 3, 6, 12 and at day 40 to ascertain any difference in SR Ca²⁺ handling before the onset of hypertension. At day 1, the rate of homogenate oxalate-supported Ca²⁺ uptake was significantly higher in SHR than in WKY (0.25 ± 0.02 vs 0.12 ± 0.01 nmoles Ca²⁺/mg wet ventricular weight/min, respectively; p < 0.001). This interstrain difference disappeared with further developmental increase in SR Ca²⁺ transport. Western Blot analysis and a semiquantitative ELISA did not reveal any difference in the amount of immunoreactive PLB (per mg of total tissue protein) between strains at any of the ages studied. In addition, levels of phosphorylated PLB formed in vitro in the presence of radiolabelled ATP and catalytic (C) subunit of protein kinase A did not differ between SHR and WKY at days 1, 3, 6 and 12. At day 40, C subunit-catalyzed formation of ³²P-PLB was reduced by 66% (p < 0.001) in SHR when compared to age-matched WKY In the early postnatal period between day 1 and 12 SR Ca²⁺-transport values were linearly related to the respective ³²P-PLB levels of both SHR and WKY rats. The results indicate that cardiac SR of SHR can sequester Ca²⁺ at a much higher rate immediately after birth compared to WKY rats. The disappearance of this interstrain difference with further development suggests that some endogenous neuroendocrine or nutritional factor(s) from the hypertensive mother may exert an influence upon the developing heart in utero resulting in a transiently advanced maturation of the SR Ca²⁺ transport function in SHR pups at the time of birth.     

Beneficial effect of enalapril in spontaneously hypertensive rats cardiac remodeling with nitric oxide synthesis blockade

Aims . To study the efficiency of an angiotensin converting enzyme inhibitor on the blood pressure (BP) and the myocardium remodeling when spontaneously hypertensive rats (SHRs) are submitted to nitric oxide synthesis (NOs) blockade (with L-NAME) and simultaneously treated.
Methods . Young adult male SHRs were separated in four groups (n = 5) and treated for 20 days: Control, L-NAME, L-NAME+Enalapril, and Enalapril. The alterations of the BP, heart mass/body mass ratio and stereological parameters for myocytes, connective tissue and intramyocardial vessels were studied among the groups.
Results . The SHRs with NOs blockade showed a great modification of the myocardium with extensive areas of reparative and interstitial fibrosis and accentuated hypertrophy of the cardiac myocytes (cross sectional area 60% higher in animals taking L-NAME than in Control SHRs). Comparing the SHRs with NO deficiency (L-NAME group), the Control SHRs and the Enalapril treated SHRs significant differences were found in the BP and in all stereological parameters. The NO deficiency caused an important BP increment in SHRs that was partially attenuated by Enalapril. This Enalapril effect was more pronounced in Control SHRs. A significant increment of the intramyocardial vessels was observed in NO deficient SHRs and Control SHRs treated with Enalapril demonstrated by the stereology (greater microvascular densities in treated SHRs).
Conclusion . Enalapril administration showed a beneficial effect on vascular remodeling and myocardial hypertrophy in SHRs. In SHRs with NO blockade, however, the beneficial effect of Enalapril occurred only in vascular remodeling.     

自发性高血压大鼠心肌和血管组织牛磺酸的转运障碍

在自发性高血压大鼠（SHR）的心肌和主动脉血管组织上观察牛磺酸（taurine)转运和牛磺酸转运体（taurine transporter,TAUT) mRNA 的改变,结果显示,与对照组WKY大鼠相比,SHR组血浆牛磺酸水平和牛磺酸释放量增加,而心肌和血管组织牛磺酸水平和TAUT mRNA含量均降低,牛磺酸最大转运速率（Vmax)分别低24％和35％（P＜0．05）,米氏常数（Km)值分别高16％和39％（P＜0．05）,这些结果提示,SHR的心肌和血管组织牛磺酸转运障碍可能与TAUT活性和亲和力降低及TAUT基因水平的下调有关。     

Gallic acid attenuates calcium calmodulin‐dependent kinase II‐induced apoptosis in spontaneously hypertensive rats

Hypertension causes cardiac hypertrophy and leads to heart failure. Apoptotic cells are common in hypertensive hearts. Ca²⁺/calmodulin‐dependent protein kinase II (CaMKII) is associated with apoptosis. We recently demonstrated that gallic acid reduces nitric oxide synthase inhibition‐induced hypertension. Gallic acid is a trihydroxybenzoic acid and has been shown to have beneficial effects, such as anti‐cancer, anti‐calcification and anti‐oxidant activity. The purpose of this study was to determine whether gallic acid regulates cardiac hypertrophy and apoptosis in essential hypertension. Gallic acid significantly lowered systolic and diastolic blood pressure in spontaneously hypertensive rats (SHRs). Wheat germ agglutinin (WGA) and H&E staining revealed that gallic acid reduced cardiac enlargement in SHRs. Gallic acid treatment decreased cardiac hypertrophy marker genes, including atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), in SHRs. The four isoforms, α, β, δ and γ, of CaMKII were increased in SHRs and were significantly reduced by gallic acid administration. Gallic acid reduced cleaved caspase‐3 protein as well as bax, p53 and p300 mRNA levels in SHRs. CaMKII δ overexpression induced bax and p53 expression, which was attenuated by gallic acid treatment in H9c2 cells. Gallic acid treatment reduced DNA fragmentation and the TUNEL positive cells induced by angiotensin II. Taken together, gallic acid could be a novel therapeutic for the treatment of hypertension through suppression of CaMKII δ‐induced apoptosis.     

Exercise intensities modulate cognitive function in spontaneously hypertensive rats through oxidative mediated synaptic plasticity in hippocampus

Oxidative damage in the brain may lead to cognitive impairments. There was considerable debate regarding the beneficial effects of physical exercise on cognitive functions because exercise protocols have varied widely across studies. We investigated whether different exercise intensities alter performance on cognitive tasks. The experiment was performed on spontaneously hypertensive rats (6 months at the established phase of hypertension) distributed into 3 groups: sedentary, low-intensity exercise and high-intensity exercise. Systolic blood pressure measurements confirmed hypertension in spontaneously hypertensive rats. In comparison to normotensive Wistar-Kyoto rats, sedentary spontaneously hypertensive rats had similar escape latencies and a similar preference for the correct quadrant in the probe trial. Compared to the sedentary group, the low-intensity exercise group had significantly better improvements in spatial memory assessed by Morris water maze. Low-intensity exercise was associated with attenuated reactive oxygen species, as measured by dihydroethidine fluorescence and nitrotyrosine staining in the dentate gyrus of the hippocampus. This was coupled with increased numbers of neurons and dendritic spines as well as a significant upregulation of synaptic density. In contrast, the beneficial effects of low-intensity exercise are abolished in high-intensity exercise as shown by increased free radical levels and an impairment in spatial memory. We concluded that exercise is an effective strategy to improve spatial memory in spontaneously hypertensive rats even at an established phase of hypertension. Low-intensity exercise exhibited better improvement on cognitive deficits than high-intensity exercise by attenuating free radical levels and improving downstream synaptic plasticity.     

Alterations of lymphocyte count and platelet volume precede cerebrovascular lesions in stroke-prone spontaneously hypertensive rats

Abstract

Background: Cerebral small vessel disease (CSVD) is associated with future stroke. Although pathological alteration in small vessels of patients with CSVD can be detected by neuroimaging, diagnosis of CSVD is delayed because it is an asymptomatic disease. The stroke-prone spontaneously hypertensive rat (SHRSP) show similar pathological features to human CSVD and develop stroke-related symptoms with advancing age.

Objective: We investigated the time course of haematological parameters in Wistar rats and SHRSP.

Material and Methods: Blood cells were analysed using an automated haematological analyser.

Results: SHRSP develop stroke-related symptoms including onset of neurological symptoms, decreased body weight and blood brain barrier leakage between 12 and 14?weeks of age. Lymphocyte counts were gradually decreased at 3?weeks before development of stoke-related symptoms and then were further decreased after the development of stroke-related symptoms. The both mean platelet volume and large platelet ratio gradually increased at 3?weeks before the development of stoke-related symptoms. However, although SHRSP showed more microcytic red cells than Wistar rats, the trajectories of change in erythrocyte-related parameters were similar between Wistar rats and SHRSP.

Conclusion: Our pilot study suggests that alterations of lymphocyte count and platelet volume predictive indicators for asymptomatic CSVD and symptomatic stroke in SHRSP.     

降血压乳酸菌发酵乳对原发性高血压大鼠的降压效果

目的对具有血管紧张素转化酶(ACE)抑制活性的乳酸菌DM9057发酵乳的抗胃肠道酶解能力及原发性高血压大鼠(SHR)体内降压效果进行研究。方法以10 ml/kg和2.5 ml/kg发酵乳一次性和连续灌胃原发性高血压大鼠。结果 DM9057发酵乳具有较好的抗胃肠道酶能力,并且2个剂量均具有较好的降血压效果,其中以10 ml/kg剂量效果最为显著,一次性和连续灌胃后,最大降压值为(17.97±3.82)、(25.46±5.06)mmHg。结论乳酸菌DM9057发酵乳具有较强的抗胃肠道能力,同时在原发性高血压大鼠体内能够发挥一定的降血压作用。     

Angiotensin-converting enzyme (kinase II) in pituitary gland of spontaneously hypertensive rats

Angiotensin-converting enzyme (ACE) (kinase II; dipeptidyl carboxypeptidase, EC 3.4.15.1) activity was measured in pituitary gland of young (4-week-old) and adult (18-week-old) male, spontaneously hypertensive rats (SHR) and in age-matched normotensive male Wistar-Kyoto (WKY) control rats. In the three lobes of the pituitary gland ACE activity was significantly higher in young than in adult animals, in both SH and WKY rats. In the anterior lobe, ACE activity was lower in SHR when compared to age-matched Wistar-Kyoto controls. In contrast, ACE activity in the intermediate lobe of the pituitary gland was higher in SHR, and in particular in young animals. The observed differences between young WKY and SH rats in both the intermediate and anterior lobes did not appear to be due to a modified affinity of ACE for the substrate hippuryl-His-Leu, but to alterations in ACE maximal velocity or number of available molecules. No differences in ACE activity were detected between SHR and WKY rats in the posterior lobe. Total protein content was higher in the intermediate lobe and lower in the posterior lobe of young SHR when compared to normotensive controls. The present results suggest the possibility for a role of pituitary ACE in spontaneous (genetic) hypertension in rats.